The long term objective of this proposal is to design, synthesize, and evaluate amphiphilic molecule made up of integrin binding motives such as Arg-Gly-Asp (RGD) tripeptide conjugated to aliphatic acid chain for enhancing the aqueous solubility and targeted delivery of anticancer drugs in cancer chemotherapy. In this project, RGD peptide will be chemically conjugated with aliphatic acids of different lengths where amine group of peptide will be linked to carboxylic acid group of alkyl acids to form amphiphilic molecule with two distinct regions of variable affinities towards a given solvent. Carbodiimide method will be used for this conjugation step. CMC of the micelles will be measured to evaluate their stability and drug loading capacity. Since RGD moieties in the micelle are exposed on the outer layers, it is hypothesized that the micelles will bind preferentially to the cancer cells via the a?[unreadable]3 integrin. The targeting efficacy of the carrier will be assessed with the cell binding assay. Affinity of their binding to cancer cells will be compared to that of normal human keratinocyte cell lines to evaluate the RGD-aliphatic acid conjugates specificity toward breast cancer cells. Binding is the first step for internalization followed by endocytosis. Cytotoxicity of the amphiphilic micelles loaded with Paclitaxel as model drug will be evaluated by qualitative and quantitative cellular uptake assays in breast carcinoma cells (HTB-129) and compared with only drug and only carrier to determine their internalization, safety, and efficacy as a drug carrier. Internalization of the amphiphiles will be evaluated using quantitative fluorescence spectroscopy and confocal microscopy. Once the feasibility is demonstrated, future studies will include optimizing the amphiphiles and testing their efficacy in animal models. Demonstration of feasibility of these carrier systems will also have broad application in delivering poorly aqueous soluble anticancer drugs. [unreadable] [unreadable] [unreadable]